Caenorhabditis elegans inhibitor of apoptosis protein (IAP) homologue BIR-1 plays a conserved role in cytokinesis
Caenorhabditis elegans inhibitor of apoptosis protein (IAP) homologue BIR-1 plays a conserved role in cytokinesis
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DOI：
10.1016/s0960-9822(99)80137-7
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发表时间：
1999-03-25
期刊：
影响因子：
9.2
通讯作者：
Hengartner, MO
中科院分区：
文献类型：
--
作者：
Fraser, AG;James, C;Hengartner, MO
背景：凋亡抑制蛋白（IAPs）在几种模型系统中抑制凋亡细胞死亡，并且在昆虫和哺乳动物之间高度保守。所有的IAP都含有至少一个类似于70个氨基酸杆状病毒IAP重复序列（BIR）的拷贝，该结构域对IAP的抗凋亡活性至关重要。然而，酵母中IAPs的显著结构多样性和含有birp的蛋白（birp）的鉴定表明：birp可能在细胞凋亡之外的其他尚未确定的细胞过程中发挥作用。Survivin是一种人类BIRP，在G2-M期上调40倍，并与有丝分裂纺锤体结合，尽管其在纺锤体中的作用尚不清楚。结果：我们鉴定并鉴定了两个秀丽隐杆线虫birp， bir1和bir2；这些蛋白是秀丽隐杆线虫中仅有的birp。bir1基因在胚胎发育过程中高度表达，在其他发育阶段均可检测到表达；bir2的表达仅在成人和胚胎中检测到。过表达bir1不能抑制秀丽隐杆线虫发育发生的细胞死亡，抑制bir1表达也不会增加细胞死亡。相反，缺少bir1的胚胎不能完成细胞分裂，变成多核的。这种细胞质分裂缺陷可以被survivin的转基因表达部分抑制，而survivin是与bir1在结构上最相关的哺乳动物BIRP，这表明BIRP在调控细胞质分裂中的保守作用。结论：秀丽隐杆线虫BIRP -1可能不参与细胞凋亡的一般调控，但在胚胎细胞分裂中是必需的。我们认为birp可能调节多种生物过程中的细胞骨架变化，包括细胞分裂和细胞凋亡。
Background: Inhibitor of apoptosis proteins (IAPs) suppress apoptotic cell death in several model systems and are highly conserved between insects and mammals. All IAPs contain at least one copy of the similar to 70 amino-acid baculovirus IAP repeat (BIR), and this domain is essential for the anti-apoptotic activity of the IAPs. Both the marked structural diversity of IAPs and the identification of BIR-containing proteins (BIRPs) in yeast, however, have led to the suggestion that: BIRPs might play roles in other, as yet unidentified, cellular processes besides apoptosis. Survivin, a human BIRP, is upregulated 40-fold at G2-M phase and binds to mitotic spindles, although its role at the spindle is still unclear.Results: We have identified and characterised two Caenorhabditis elegans BIRPs, BIR-1 and BIR-2; these proteins are the only BIRPs in C. elegans. The bir-1 gene is highly expressed during embryogenesis with detectable expression throughout other stages of development; bir-2 expression is detectable only in adults and embryos. Overexpression of bir-1 was unable to inhibit developmentally occurring cell death in C. elegans and inhibition of bir-1 expression did not increase cell death. Instead, embryos lacking bir-1 were unable to complete cytokinesis and they became multinucleate. This cytokinesis defect could be partially suppressed by transgenic expression of survivin, the mammalian BIRP most structurally related to BIR-1,suggesting a conserved role for BIRPs in the regulation of cytokinesis.Conclusions: BIR-1, a C. elegans BIRP, is probably not involved in the general regulation of apoptosis but is required for embryonic cytokinesis. We suggest that BIRPs may regulate cytoskeletal changes in diverse biological processes including cytokinesis and apoptosis.